Due to the presence of artifacts induced by fast-imaging acquisition in functional magnetic resonance imaging (fMRI) studies, it is very difficult to estimate the variance of thermal noise by traditional methods in magnitude images. Moreover, the existence of incidental phase fluctuations impairs the validity of currently available solutions based on complex datasets. In this article, a time-domain model is proposed to generalize the analysis of complex datasets for nonbrain regions by incorporating artifacts and phase fluctuations. Based on this model, a novel estimation schema has been developed to find an appropriate set of voxels in nonbrain regions according to their levels of artifact and phase fluctuation. In addition, noise intensity from these voxels is estimated. The whole schema is named COmplex-Model-Based Estimation (COMBE). Theoretical and experimental results demonstrate that the proposed COMBE method provides a better estimation of thermal noise in fMRI studies compared with previously proposed methods and suggest that the new method can adapt to a broader range of applications, such as functional connectivity studies, evaluation of sequence designs and reconstruction schemas.